Examples of Nephrotoxicants

As with toxicity in other organs the ultimate expression of a toxic end point is the result of a balance between the generation of reactive metabolites and their detoxication. The high levels of glutathione found in the kidney doubtless play an important role in the detoxication process. 

Cadmium has a long biological half-life, 10 to 12 years in humans thus low-level chronic exposure will eventually result in accumulation to toxic concentrations. 

as Pb2+, is taken up readily by proximal tubule cells, where it damages mitochondria and inhibits mitochondrial function, altering the normal absorptive functions of the cell. Complexes of lead with acidic proteins appear as inclusion bodies in the nuclei of tubular epithelium cells. These bodies, formed before signs of lead toxicity occur, appear to serve as a protective mechanism. 

Mercury. Mercury exerts its principle nephrotoxic effect on the membrane of the proximal tubule cell. In low concentrations, mercury binds to the sulfhydryl groups of membrane proteins and acts as a diuretic by inhibiting sodium reabsorption. Organomer-curial diuretics were introduced into clinical practice in the 1920s and were used 

Uranium. About 50% of plasma uranium is bound, as the uranyl ion, to bicarbonate, which is filtered by the glomerulus. As a result of acidification in the proximal tubule, the bicarbonate complex dissociates, followed by reabsorption of the bicarbonate ion the released UO22 1 then becomes attached to the membrane of the proximal tubule cells. The resultant loss of cell function is evidenced by increased concentrations of glucose, amino acids, and proteins in the urine. 

---